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Pharmacokinetics > Pharmacokinetics - Metabolism > Flashcards

Pharmacokinetics - Metabolism Flashcards

1
Q

3 major routes involved in elimination:

A
  1. Hepatic Metabolism
  2. Elimination in bile
  3. Elimination in urine
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2
Q

What is clearance?

A

Clearance (CL) estimates the amount of drug cleared from the body per unit of time

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3
Q

How is total clearance calculated?

A

CL = 0.693 × Vd
_____
t1/2

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4
Q

Give Michaelis-Menten Equation for 1st order kinetics

A

v = rate of drug metabolism= V max (C)
—————-
Km

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5
Q

What is first order kinetics?

A

The rate of drug metabolism and elimination is directly proportional to the concentration of free drug

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6
Q

First-order kinetics is sometimes referred to clinically as __________

A

linear kinetics

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7
Q

In First Order Kinetics, with every half-life the

concentration reduces by ______.

A

50%

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8
Q

Give Michaelis-Menten Equation for zero order kinetics

A

v = rate of drug metabolism = Vmax

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9
Q

Give drugs that show zero order kinetics.

A

aspirin, ethanol , phenytoin

the doses are very large

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10
Q

What is zero order kinetics?

A

The enzyme is saturated by a high free-drug concentration, and the rate of metabolism remains constant over time.

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11
Q

Zero-order kinetics is sometimes referred to clinically as __________

A

Non-linear kinetics

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12
Q

The ______ cannot efficiently eliminate lipophilic drugs that readily cross cell membranes and are reabsorbed in the distal convoluted tubules

A

kidney

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13
Q

Lipid-soluble agents must first be metabolized into

more _______ substances in the liver using two general sets of reactions, called Phase I and Phase II

A

polar (hydrophilic)

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14
Q

_________ reactions convert lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group, such as –OH or –NH2.

A

Phase I

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15
Q

Phase I metabolism may have which effect on the drug’s pharmacologic activity?

a. increase
b. decrease
c. leave unaltered
d. All of the above

A

d. All of the above

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16
Q

The Phase I reactions most frequently involved in drug metabolism are catalyzed by the ______system

A

cytochrome P450

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17
Q

cytochrome P450 is also called _______

A

microsomal mixed-function oxidases

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18
Q

The P450 system is important for:

A
  1. The metabolism of many endogenous compounds (such as steroids, lipids, etc.
  2. The biotransformation of exogenous substances (xenobiotics)
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19
Q

Cytochrome P450, designated as CYP, is a superfamily of ________that are located in most cells but are
primarily found in the liver and GI tract.

A

heme-containing isozymes

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20
Q

Define nomenclature for Cytochrome P450 enzymes.

A

The family name is indicated by CYP added to
an arabic number, followed by a capital letter for the subfamily,
for example, CYP3A
Another number is added to indicate the specific isozyme, as in CYP3A4

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21
Q

There are many different P450 ______

A

isoforms

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22
Q

Four isozymes are responsible for the vast majority of P450-catalyzed reactions. They are :

A

CYP3A4/5
CYP2D6,
CYP2C8/9,
and CYP1A2

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23
Q

Considerable amounts of
______ are found in intestinal mucosa, accounting for the first-pass metabolism of drugs such as chlorpromazine and clonazepam.

A

CYP3A4

24
Q

P450 enzymes exhibit considerable

genetic variability among individuals and ______

A

racial groups

25
Q

______, in particular, has been

shown to exhibit genetic polymorphism

A

CYP2D6

26
Q

_______ mutations result in very low capacities to metabolize substrates

A

CYP2D6

27
Q

Patients who are poor CYP2C19 metabolizers

have a higher incidence of cardiovascular events (for example, stroke or myocardial infarction) when taking _________

A

clopidogrel

28
Q

Clopidogrel is a ______ and CYP2C19 activation is required to convert it to its (active) metabolite

A

Prodrug

29
Q

no polymorphisms have been identified so far for this P450 isozyme.

A

CYP3A4

30
Q

Some individuals obtain no benefit from the opioid analgesic codeine, because they lack the _____enzyme that O-demethylates and activates the drug

A

CYP2D6

31
Q

The frequency of CYP2D6 polymorphism is in part racially determined.
It’s prevalence in European Caucasians is:
It’s prevalence in Southeast Asians is:

A

5 to 10 % in European Caucasians

Less than 2% in Southeast Asians

32
Q

Isozyme CYP 2C9/10 Substrate drugs:

A

Warfarin
Phenytoin
Ibuprofen
Tolbutamide

33
Q

Isozyme CYP 2C9/10 Inducers:

A

Phenobarbital

Rifampin

34
Q

Isozyme CYP 2D6 Substrate drugs:

A

Desipramine
Imipramine
Haloperidol
Propranolol

35
Q

Isozyme CYP 3A4/5 Substrate drugs:

A 
Carbamazepine
Cyclosporine
Erythromycin
Clarithromycin
Nifedipine
Verapamil
Simvastatin
36
Q

Isozyme CYP 3A4/5 Inducers:

A 
Carbamazepine
Dexamethasone
Phenobarbital
Phenytoin
Rifampin
37
Q

What are CYP Isozyme Inducers:

A

Certain drugs are capable of increasing the synthesis of one or more CYP isozymes.
This results in increased biotransformation of drugs
and significant decreases in plasma concentrations, with concurrent loss of pharmacologic effect.

38
Q

Rifampin, an antituberculosis drug, significantly decreases the plasma concentrations of_________.

A

HIV protease inhibitors

39
Q

HIV protease inhibitors role:

A

suppress HIV virion maturation

40
Q

Omeprazole is a potent inhibitor of three of the CYP

isozymes responsible for ______ metabolism

A

warfarin

41
Q

If the Omeprazole and Warfarin are taken together:

A

Plasma concentrations of warfarin increase,

which leads to greater inhibition of coagulation and risk of hemorrhage and other serious bleeding reactions.

42
Q

Name important CYP inhibitors:

A

erythromycin
ketoconazole,
ritonavir
(because they each inhibit several CYP isozymes)

43
Q

_____ blocks the metabolism of theophylline, clozapine and warfarin

A

Cimetidine

44
Q

Why Grapefruit is contraindicated with Simvastatin?

A

Grapefruit and its juice inhibits CYP3A4.
Drugs such as nifedipine, clarithromycin, and simvastatin, are metabolized by this system,
(higher blood levels and the potential to increase the drugs’ therapeutic and/or toxic effects)

45
Q

Phase I reactions not involving the P450 system:

A
  1. Amine oxidation e.g. oxidation of catecholamines or
    histamine
  2. Alcohol dehydrogenation e.g. ethanol
    oxidation
  3. Esterases e.g. metabolism of pravastatin in
    liver
  4. Hydrolysis e.g. of procaine
46
Q

Phase II consists of ______ reactions

A

conjugation

47
Q

If the metabolite from Phase I metabolism is sufficiently ______, it can be excreted by the kidneys.

A

Polar

48
Q

Conjugation reaction with the following groups results in polar, usually more water-soluble compounds that are most often therapeutically inactive.

A

glucuronic acid
sulfuric acid
acetic acid
amino acid

49
Q

_________is the most common and the most important conjugation reaction

A

Glucuronidation

50
Q

Glucuronidation renders the drug inactive. A notable exception to glucuronidation is :

A

morphine-6-glucuronide ,

which is more potent than morphine

51
Q

_______ are deficient in this conjugating system

A

Neonates

52
Q

Why Chloramphenicol is not given to neonates?

A

chloramphenicol is inactivated by the
addition of glucuronic acid.
Since Neonates are deficient in this conjugating system, it results in gray baby syndrome.

53
Q

Drugs already possessing these groups may enter Phase II directly and become conjugated without prior Phase I metabolism

A

–OH, –NH2, or –COOH

54
Q

The highly polar drug conjugates may be excreted by :

A

the kidney or in bile

55
Q

Not all drugs undergo Phase I and

II reactions in that order. Give example

A

Isoniazid is first acetylated (a Phase II reaction) and then hydrolyzed to isonicotinic acid (a Phase I reaction)

Pharmacokinetics (5 decks)

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